Authors:A.T.W.M. Hendriks; J.B. van Lier; M.K. de KreukPages: 1 - 13Abstract: Publication date: January–February 2018 Source:Biotechnology Advances, Volume 36, Issue 1 Author(s): A.T.W.M. Hendriks, J.B. van Lier, M.K. de Kreuk Fermentation and anaerobic digestion of organic waste and wastewater is broadly studied and applied. Despite widely available results and data for these processes, comparison of the generated results in literature is difficult. Not only due to the used variety of process conditions, but also because of the many different growth media that are used. Composition of growth media can influence biogas production (rates) and lead to process instability during anaerobic digestion. To be able to compare results of the different studies reported, and to ensure nutrient limitation is not influencing observations ascribed to process dynamics and/or reaction kinetics, a standard protocol for creating a defined growth medium for anaerobic digestion and mixed culture fermentation is proposed. This paper explains the role(s) of the different macro- and micronutrients, as well as the choices for a growth medium formulation strategy. In addition, the differences in nutrient requirements between mesophilic and thermophilic systems are discussed as well as the importance of specific trace metals regarding specific conversion routes and the possible supplementary requirement of vitamins. The paper will also give some insight into the bio-availability and toxicity of trace metals. A remarkable finding is that mesophilic and thermophilic enzymes are quite comparable at their optimum temperatures. This has consequences for the trace metal requirements of thermophiles under certain conditions. Under non-limiting conditions, the trace metal requirement of thermophilic systems is about 3 times higher than for mesophilic systems.

Authors:Martina D'Este; Merlin Alvarado-Morales; Irini AngelidakiPages: 14 - 25Abstract: Publication date: January–February 2018 Source:Biotechnology Advances, Volume 36, Issue 1 Author(s): Martina D'Este, Merlin Alvarado-Morales, Irini Angelidaki Amino acids are attractive and promising biochemicals with market capacity requirements constantly increasing. Their applicability ranges from animal feed additives, flavour enhancers and ingredients in cosmetic to specialty nutrients in pharmaceutical and medical fields. This review gives an overview of the processes applied for amino acids production and points out the main advantages and disadvantages of each. Due to the advances made in the genetic engineering techniques, the biotechnological processes, and in particular the fermentation with the aid of strains such as Corynebacterium glutamicum or Escherichia coli, play a significant role in the industrial production of amino acids. Despite the numerous advantages of the fermentative amino acids production, the process still needs significant improvements leading to increased productivity and reduction of the production costs. Although the production processes of amino acids have been extensively investigated in previous studies, a comprehensive overview of the developments in bioprocess technology has not been reported yet. This review states the importance of the fermentation process for industrial amino acids production, underlining the strengths and the weaknesses of the process. Moreover, the potential of innovative approaches utilizing macro and microalgae or bacteria are presented.

Authors:Loris Fossier Marchan; Kim J. Lee Chang; Peter D. Nichols; Wilfrid J. Mitchell; Jane L. Polglase; Tony GutierrezPages: 26 - 46Abstract: Publication date: January–February 2018 Source:Biotechnology Advances, Volume 36, Issue 1 Author(s): Loris Fossier Marchan, Kim J. Lee Chang, Peter D. Nichols, Wilfrid J. Mitchell, Jane L. Polglase, Tony Gutierrez Thraustochytrids were first discovered in 1934, and since the 1960's they have been increasingly studied for their beneficial and deleterious effects. This review aims to provide an enhanced understanding of these protists with a particular emphasis on their taxonomy, ecology and biotechnology applications. Over the years, thraustochytrid taxonomy has improved with the development of modern molecular techniques and new biochemical markers, resulting in the isolation and description of new strains. In the present work, the taxonomic history of thraustochytrids is reviewed, while providing an up-to-date classification of these organisms. It also describes the various biomarkers that may be taken into consideration to support taxonomic characterization of the thraustochytrids, together with a review of traditional and modern techniques for their isolation and molecular identification. The originality of this review lies in linking taxonomy and ecology of the thraustochytrids and their biotechnological applications as producers of docosahexaenoic acid (DHA), carotenoids, exopolysaccharides and other compounds of interest. The paper provides a summary of these aspects while also highlighting some of the most important recent studies in this field, which include the diversity of polyunsaturated fatty acid metabolism in thraustochytrids, some novel strategies for biomass production and recovery of compounds of interest. Furthermore, a detailed overview is provided of the direct and current applications of thraustochytrid-derived compounds in the food, fuel, cosmetic, pharmaceutical, and aquaculture industries and of some of the commercial products available. This review is intended to be a source of information and references on the thraustochytrids for both experts and those who are new to this field.

Authors:Hsiao-Han Lin; Bak-Sau Yip; Li-Min Huang; Suh-Chin WuPages: 47 - 53Abstract: Publication date: January–February 2018 Source:Biotechnology Advances, Volume 36, Issue 1 Author(s): Hsiao-Han Lin, Bak-Sau Yip, Li-Min Huang, Suh-Chin Wu The growing number of zika virus (ZIKV) infections plus a 20-fold increase in neonatal microcephaly in newborns in Brazil have raised alarms in many countries regarding the threat to pregnant women. Instances of microcephaly and central nervous system malformations continue to increase in ZIKV outbreak regions. ZIKV is a small enveloped positive-strand RNA virus belonging to the Flavivirus genus of the Flaviviridae family. High-resolution ZIKV structures recently identified by cryo-electron microscopy indicate that the overall ZIKV structure is similar to those of other flaviviruses. With its compact surface, ZIKV is more thermally stable than the dengue virus (DENV). ZIKV E proteins have a characteristic “herringbone” structure with a single glycosylation site. The ZIKV E protein, the major protein involved in receptor binding and fusion, is formed as a head-to-tail dimer on the surfaces of viral particles. The E monomer consists of three distinct domains: DI, DII, and DIII. The finger-like DII contains a fusion loop (FL) that is inserted into the host cell endosomal membrane during pH-dependent conformational changes that drive fusion. Quaternary E:E dimer epitopes located at the interaction site of prM and E dimers can be further divided into two dimer epitopes. To date, more than 50 ZIKV vaccine candidates are now in various stages of research and development. Candidate ZIKV vaccines that are currently in phase I/II clinical trials include inactivated whole viruses, recombinant measles viral vector-based vaccines, DNA and mRNA vaccines, and a mosquito salivary peptide vaccine. Stabilized forms of ZIKV E:E dimer proteins have been successfully obtained either by introducing additional inter-subunit disulfide bond(s) in DII or via the direct assembly of E:E dimer proteins by immobilization with monomeric E proteins. The VLP-based approach is another alternative method for presenting native E:E dimer antigens among the vaccine components. Several forms of ZIKV VLPs have been reported featuring the co-expression of the prM-E, prM-E-NS1, C-prM-E, and NS2B/NS3 viral genes in human cells. To minimize the effect of the cross-reactive ADE-facilitating antibodies between ZIKV and DENV, several novel mutations have been reported either in or near the FL of DII or DIII to dampen the production of cross-reactive antibodies. Future ZIKV vaccine design efforts should be focused on eliciting improved neutralizing antibodies with a reduced level of cross-reactivity to confer sterilizing immunity.

Authors:Jianjun Hu; Dillirani Nagarajan; Quanguo Zhang; Jo-Shu Chang; Duu-Jong LeePages: 54 - 67Abstract: Publication date: January–February 2018 Source:Biotechnology Advances, Volume 36, Issue 1 Author(s): Jianjun Hu, Dillirani Nagarajan, Quanguo Zhang, Jo-Shu Chang, Duu-Jong Lee Pigments (mainly carotenoids) are important nutraceuticals known for their potent anti-oxidant activities and have been used extensively as high end health supplements. Microalgae are the most promising sources of natural carotenoids and are devoid of the toxic effects associated with synthetic derivatives. Compared to photoautotrophic cultivation, heterotrophic cultivation of microalgae in well-controlled bioreactors for pigments production has attracted much attention for commercial applications due to overcoming the difficulties associated with the supply of CO2 and light, as well as avoiding the contamination problems and land requirements in open autotrophic culture systems. In this review, the heterotrophic metabolic potential of microalgae and their uses in pigment production are comprehensively described. Strategies to enhance pigment production under heterotrophic conditions are critically discussed and the challenges faced in heterotrophic pigment production with possible alternative solutions are presented.

Authors:Hossein Salehizadeh; Ning Yan; Ramin FarnoodPages: 92 - 119Abstract: Publication date: January–February 2018 Source:Biotechnology Advances, Volume 36, Issue 1 Author(s): Hossein Salehizadeh, Ning Yan, Ramin Farnood Natural polysaccharides, derived from biomass feedstocks, marine resources, and microorganisms, have been attracting considerable attention as benign and environmentally friendly substitutes for synthetic polymeric products. Besides many other applications, these biopolymers are rapidly emerging as viable alternatives to harmful synthetic flocculating agents for the removal of contaminants from water and wastewater. In recent years, a great deal of effort has been devoted to improve the production and performance of polysaccharide bio-based flocculants. In this review, current trends in preparation and chemical modification of polysaccharide bio-based flocculants and their flocculation performance are discussed. Aspects including mechanisms of flocculation, biosynthesis, classification, purification and characterization, chemical modification, the effect of physicochemical factors on flocculating activity, and recent applications of polysaccharide bio-based flocculants are summarized and presented.

Authors:Yan-Ru Lou; Alan W. LeungPages: 132 - 149Abstract: Publication date: January–February 2018 Source:Biotechnology Advances, Volume 36, Issue 1 Author(s): Yan-Ru Lou, Alan W. Leung Organoids are in vitro cultures of miniature fetal or adult organ-like structures. Their potentials for use in tissue and organ replacement, disease modeling, toxicology studies, and drug discovery are tremendous. Currently, major challenges facing human organoid technology include (i) improving the range of cellular heterogeneity for a particular organoid system, (ii) mimicking the native micro- and matrix-environment encountered by cells within organoids, and (iii) developing robust protocols for the in vitro maturation of organoids that remain mostly fetal-like in cultures. To tackle these challenges, we advocate the principle of reverse engineering that replicates the inner workings of in vivo systems with the goal of achieving functionality and maturation of the resulting organoid structures with the input of minimal intrinsic (cellular) and environmental (matrix and niche) constituents. Here, we present an overview of organoid technology development in several systems that employ cell materials derived from fetal and adult tissues and pluripotent stem cell cultures. We focus on key studies that exploit the self-organizing property of embryonic progenitors and the role of designer matrices and cell-free scaffolds in assisting organoid formation. We further explore the relationship between adult stem cells, niche factors, and other current developments that aim to enhance robust organoid maturation. From these works, we propose a standardized pipeline for the development of future protocols that would help generate more physiologically relevant human organoids for various biomedical applications.

Authors:Vinod Kumar; Sunghoon ParkPages: 150 - 167Abstract: Publication date: January–February 2018 Source:Biotechnology Advances, Volume 36, Issue 1 Author(s): Vinod Kumar, Sunghoon Park Klebsiella pneumoniae is a Gram-negative facultative anaerobe that metabolizes glycerol efficiently under both aerobic and anaerobic conditions. This microbe is considered an outstanding biocatalyst for transforming glycerol into a variety of value-added products. Crude glycerol is a cheap carbon source and can be converted by K. pneumoniae into useful compounds such as lactic acid, 3-hydroxypropionic acid, ethanol, 1,3-propanediol, 2,3-butanediol, and succinic acid. This review summarizes glycerol metabolism in K. pneumoniae and its potential as a microbial cell factory for the production of commercially important acids and alcohols. Although many challenges remain, K. pneumoniae is a promising workhorse when glycerol is used as the carbon source.

Authors:H. Edward Wong; Chung-Jr Huang; Zhongqi ZhangPages: 168 - 181Abstract: Publication date: January–February 2018 Source:Biotechnology Advances, Volume 36, Issue 1 Author(s): H. Edward Wong, Chung-Jr Huang, Zhongqi Zhang Proteins provide the molecular basis for cellular structure, catalytic activity, signal transduction, and molecular transport in biological systems. Recombinant protein expression is widely used to prepare and manufacture novel proteins that serve as the foundation of many biopharmaceutical products. However, protein translation bioprocesses are inherently prone to low-level errors. These sequence variants caused by amino acid misincorporation have been observed in both native and recombinant proteins. Protein sequence variants impact product quality, and their presence can be exacerbated through cellular stress, overexpression, and nutrient starvation. Therefore, the cell line selection process, which is used in the biopharmaceutical industry, is not only directed towards maximizing productivity, but also focuses on selecting clones which yield low sequence variant levels, thereby proactively avoiding potentially inauspicious patient safety and efficacy outcomes. Here, we summarize a number of hallmark studies aimed at understanding the mechanisms of amino acid misincorporation, as well as exacerbating factors, and mitigation strategies. We also describe key advances in analytical technologies in the identification and quantification of sequence variants, and some practical considerations when using LC-MS/MS for detecting sequence variants.

Authors:Zhiliang Yang; Zisheng ZhangPages: 182 - 195Abstract: Publication date: January–February 2018 Source:Biotechnology Advances, Volume 36, Issue 1 Author(s): Zhiliang Yang, Zisheng Zhang Pichia pastoris has been recognized as one of the most industrially important hosts for heterologous protein production. Despite its high protein productivity, the optimization of P. pastoris cultivation is still imperative due to strain- and product-specific challenges such as promoter strength, methanol utilization type and oxygen demand. To address the issues, strategies involving genetic and process engineering have been employed. Optimization of codon usage and gene dosage, as well as engineering of promoters, protein secretion pathways and methanol metabolic pathways have proved beneficial to innate protein expression levels. Large-scale production of proteins via high cell density fermentation additionally relies on the optimization of process parameters including methanol feed rate, induction temperature and specific growth rate. Recent progress related to the enhanced production of proteins in P. pastoris via various genetic engineering and cultivation strategies are reviewed. Insight into the regulation of the P. pastoris alcohol oxidase 1 (AOX1) promoter and the development of methanol-free systems are highlighted. Novel cultivation strategies such as mixed substrate feeding are discussed. Recent advances regarding substrate and product monitoring techniques are also summarized. Application of P. pastoris to the production of biodiesel and other value-added products via metabolic engineering are also reviewed. P. pastoris is becoming an indispensable platform through the use of these combined engineering strategies.

Authors:Joana Gangoiti; Tjaard Pijning; Lubbert DijkhuizenPages: 196 - 207Abstract: Publication date: January–February 2018 Source:Biotechnology Advances, Volume 36, Issue 1 Author(s): Joana Gangoiti, Tjaard Pijning, Lubbert Dijkhuizen Transglucosidases belonging to the glycoside hydrolase (GH) family 70 are promising enzymatic tools for the synthesis of α-glucans with defined structures from renewable sucrose and starch substrates. Depending on the GH70 enzyme specificity, α-glucans with different structures and physicochemical properties are produced, which have found diverse (potential) commercial applications, e.g. in food, health and as biomaterials. Originally, the GH70 family was established only for glucansucrase enzymes of lactic acid bacteria that catalyze the synthesis of α-glucan polymers from sucrose. In recent years, we have identified 3 novel subfamilies of GH70 enzymes (designated GtfB, GtfC and GtfD), inactive on sucrose but converting starch/maltodextrin substrates into novel α-glucans. These novel starch-acting enzymes considerably enlarge the panel of α-glucans that can be produced. They also represent very interesting evolutionary intermediates between sucrose-acting GH70 glucansucrases and starch-acting GH13 α-amylases. Here we provide an overview of the repertoire of GH70 enzymes currently available with focus on these novel starch-acting GH70 enzymes and their biotechnological potential. Moreover, we discuss key developments in the understanding of structure-function relationships of GH70 enzymes in the light of available three-dimensional structures, and the protein engineering strategies that were recently applied to expand their natural product specificities.

Authors:Luís A. Rocha; David A. Learmonth; Rui A. Sousa; António J. SalgadoPages: 208 - 227Abstract: Publication date: January–February 2018 Source:Biotechnology Advances, Volume 36, Issue 1 Author(s): Luís A. Rocha, David A. Learmonth, Rui A. Sousa, António J. Salgado Integrins are cell adhesion receptors predominantly important during normal and tumor angiogenesis. A sequence present on several extracellular matrix proteins composed of Arg-Gly-Asp (RGD) has attracted attention due to its role in cell adhesion mediated by integrins. The development of ligands that can bind to integrins involved in tumor angiogenesis and brake disease progression has resulted in new investigational drug entities reaching the clinical trial phase in humans. The use of integrin-specific ligands can be useful for the vascularization of regenerative medicine constructs, which remains a major limitation for translation into clinical practice. In order to enhance vascularization, immobilization of integrin-specific RGD peptidomimetics within constructs is a recommended approach, due to their high specificity and selectivity towards certain desired integrins. This review endeavours to address the potential of peptidomimetic-coated biomaterials as vascular network promoters for regenerative medicine purposes. Clinical studies involving molecules tracking active integrins in cancer angiogenesis and reasons for their failure are also addressed.

Authors:Kathleen Balke; Andy Beier; Uwe T. BornscheuerPages: 247 - 263Abstract: Publication date: January–February 2018 Source:Biotechnology Advances, Volume 36, Issue 1 Author(s): Kathleen Balke, Andy Beier, Uwe T. Bornscheuer Baeyer-Villiger monooxygenases (BVMOs) are versatile biocatalysts for the conversion of ketones to lactones or esters while also being able to efficiently oxidize sulfides to sulfoxides. However, there are limitations for the application of BVMOs in synthesis. In this review we provide an overview of the protein engineering studies aiming at optimizing different properties of BVMOs. We describe hot spots in the active sites of certain BVMOs that have been successfully targeted for changing the substrate scope, as well as the possibility to influence this property by allosteric effects. The identified hot spots in the active sites for controlling enantio- and regioselectivity are shown to be transferable to other BVMOs and we describe concepts to influence heteroatom oxidation, improve protein stability and change the cofactor dependency of BVMOs. Summarizing all these different studies enabled the identification of BVMO- or property-dependent as well as universal hot spots.

Authors:Ahmed Mahas; C. Neal Stewart; Magdy M. MahfouzPages: 295 - 310Abstract: Publication date: January–February 2018 Source:Biotechnology Advances, Volume 36, Issue 1 Author(s): Ahmed Mahas, C. Neal Stewart, Magdy M. Mahfouz Genome editing has enabled broad advances and novel approaches in studies of gene function and structure; now, emerging methods aim to precisely engineer post-transcriptional processes. Developing precise, efficient molecular tools to alter the transcriptome holds great promise for biotechnology and synthetic biology applications. Different approaches have been employed for targeted degradation of RNA species in eukaryotes, but they lack programmability and versatility, thereby limiting their utility for diverse applications. The CRISPR/Cas9 system has been harnessed for genome editing in many eukaryotic species and, using a catalytically inactive Cas9 variant, the CRISPR/dCas9 system has been repurposed for transcriptional regulation. Recent studies have used other CRISPR/Cas systems for targeted RNA degradation and RNA-based manipulations. For example, Cas13a, a Type VI-A endonuclease, has been identified as an RNA-guided RNA ribonuclease and used for manipulation of RNA. Here, we discuss different modalities for targeted RNA interference with an emphasis on the potential applications of CRISPR/Cas systems as programmable transcriptional regulators for broad uses, including functional biology, biotechnology, and synthetic biology applications.

Authors:Shirin Soleimani; Milad Shamsi; Mehran Akbarpour Ghazani; Hassan Pezeshgi Modarres; Karolina Papera Valente; Mohsen Saghafian; Mehdi Mohammadi Ashani; Mohsen Akbari; Amir Sanati-NezhadAbstract: Publication date: Available online 5 March 2018 Source:Biotechnology Advances Author(s): Shirin Soleimani, Milad Shamsi, Mehran Akbarpour Ghazani, Hassan Pezeshgi Modarres, Karolina Papera Valente, Mohsen Saghafian, Mehdi Mohammadi Ashani, Mohsen Akbari, Amir Sanati-Nezhad Emerging evidence shows that endothelial cells are not only the building blocks of vascular networks that enable oxygen and nutrient delivery throughout a tissue but also serve as a rich resource of angiocrine factors. Endothelial cells play key roles in determining cancer progression and response to anti-cancer drugs. Furthermore, the endothelium-specific deposition of extracellular matrix is a key modulator of the availability of angiocrine factors to both stromal and cancer cells. Considering tumor vascular network as a decisive factor in cancer pathogenesis and treatment response, these networks need to be an inseparable component of cancer models. Both computational and in vitro experimental models have been extensively developed to model tumor-endothelium interactions. While informative, they have been developed in different communities and do not yet represent a comprehensive platform. In this review, we overview the necessity of incorporating vascular networks for both in vitro and in silico cancer models and discuss recent progresses and challenges of in vitro experimental microfluidic cancer vasculature-on-chip systems and their in silico counterparts. We further highlight how these two approaches can merge together with the aim of presenting a predictive combinatorial platform for studying cancer pathogenesis and testing the efficacy of single or multi-drug therapeutics for cancer treatment.

Authors:Ganesh V. Halade; Laurence M. Black; Mahendra Kumar VermaAbstract: Publication date: Available online 28 February 2018 Source:Biotechnology Advances Author(s): Ganesh V. Halade, Laurence M. Black, Mahendra Kumar Verma Fatty acid drug discovery (FADD) is defined as the identification of novel, specialized bioactive mediators that are derived from fatty acids and have precise pharmacological/therapeutic potential. A number of reports indicate that dietary intake of omega-3 fatty acids and limited intake of omega-6 promotes overall health benefits. In 1929, Burr and Burr indicated the significant role of essential fatty acids for survival and functional health of many organs. In reference to specific dietary benefits of differential omega-3 fatty acids, docosahexaenoic and eicosapentaenoic acids (DHA and EPA) are transformed to monohydroxy, dihydroxy, trihydroxy, and other complex mediators during infection, injury, and exercise to resolve inflammation. The presented FADD approach describes the metabolic transformation of DHA and EPA in response to injury, infection, and exercise to govern uncontrolled inflammation. Metabolic transformation of DHA and EPA into a number of pro-resolving molecules exemplifies a novel, inexpensive approach compared to traditional, expensive drug discovery. DHA and EPA have been recommended for prevention of cardiovascular disease since 1970. Therefore, the FADD approach is relevant to cardiovascular disease and resolution of inflammation in many injury models. Future research demands identification of novel action targets, receptors for biomolecules, mechanism(s), and drug-interactions with resolvins in order to maintain homeostasis.

Authors:Rohit Kumar; Shalini Mukherjee; Belay T. AyeleAbstract: Publication date: Available online 28 February 2018 Source:Biotechnology Advances Author(s): Rohit Kumar, Shalini Mukherjee, Belay T. Ayele Wheat is one of the most important crops globally, and its grain is mainly used for human food, accounting for 20% of the total dietary calories. It is also used as animal feed and as a raw material for a variety of non-food and non-feed industrial products such as a feedstock for the production of bioethanol. Starch is the major constituent of a wheat grain, as a result, it is considered as a critical determinant of wheat yield and quality. The amount and composition of starch deposited in wheat grains is controlled primarily by sucrose transport from source tissues to the grain and its conversion to starch. Therefore, elucidation of the molecular mechanisms regulating these physiological processes provides important opportunities to improve wheat starch yield and quality through biotechnological approaches. This review comprehensively discusses the current understanding of the molecular aspects of sucrose transport and sucrose-to-starch metabolism in wheat grains. It also highlights the advances and prospects of starch biotechnology in wheat.

Authors:Fatemeh Farjadian; Mohsen Moghoofei; Soroush Mirkiani; Amir Ghasemi; Navid Rabiee; Shima Hadifar; Ali Beyzavi; Mahdi Karimi; Michael R. HamblinAbstract: Publication date: Available online 28 February 2018 Source:Biotechnology Advances Author(s): Fatemeh Farjadian, Mohsen Moghoofei, Soroush Mirkiani, Amir Ghasemi, Navid Rabiee, Shima Hadifar, Ali Beyzavi, Mahdi Karimi, Michael R. Hamblin Drug delivery is a rapidly growing area of research motivated by the nanotechnology revolution, the ideal of personalized medicine, and the desire to reduce the side effects of toxic anti-cancer drugs. Amongst a bewildering array of different nanostructures and nanocarriers, those examples that are fundamentally bio-inspired and derived from natural sources are particularly preferred. Delivery of vaccines is also an active area of research in this field. Bacterial cells and their components that have been used for drug delivery, include the crystalline cell-surface layer known as “S-layer”, bacterial ghosts, bacterial outer membrane vesicles, and bacterial products or derivatives (e.g. spores, polymers, and magnetic nanoparticles). Considering the origin of these components from potentially pathogenic microorganisms, it is not surprising that they have been applied for vaccines and immunization. The present review critically summarizes their applications focusing on their advantages for delivery of drugs, genes, and vaccines.

Authors:Lukasz Huminieck; Jarosław HorbańczukAbstract: Publication date: Available online 22 February 2018 Source:Biotechnology Advances Author(s): Lukasz Huminieck, Jarosław Horbańczuk Resveratrol has anti-cancer effects in vitro, and hypothetical chemopreventive effects in vivo. Effects are pleiotropic, mediated by changes in expression of many genes and epigenetic reprogramming. Thus, they are well suited for functional genomic studies. We carried out systematic review of such studies (reflecting also on technological progress). Differentially expressed genes commonly linked to resveratrol treatment were linked to cell cycle, proliferation, and apoptosis. However, it is unclear if these are primary and specific targets of resveratrol. We conclude by discussing areas where additional functional genomic studies are desirable, including experiments that better model in vivo effects of dietary intake.

Authors:Yunpeng Yang; Xiaoqun Nie; Yuqian Jiang; Chen Yang; Yang Gu; Weihong JiangAbstract: Publication date: Available online 22 February 2018 Source:Biotechnology Advances Author(s): Yunpeng Yang, Xiaoqun Nie, Yuqian Jiang, Chen Yang, Yang Gu, Weihong Jiang Solventogenic clostridia, a group of important industrial microorganisms, have exceptional substrate and product diversity, capable of producing a series of two-carbon and even long-chain chemicals and fuels by using various substrates, including sugars, cellulose and hemicellulose, and C1 gases. For the sake of in-depth understanding and engineering these anaerobic microorganisms for broader applications, studies on metabolic regulation of solventogenic clostridia had been extensively carried out during the past ten years, based on the rapid development of various genetic tools. To date, a number of regulators that are essential for cell physiological and metabolic processes have been identified in clostridia, and the relevant mechanisms have also been dissected, providing a wealth of valuable information for metabolic engineering. Here, we reviewed the latest research progress on the metabolic regulation for chemical production and carbohydrate utilization in solventogenic clostridia, by focusing on three typical Clostridium species, the saccharolytic C. acetobutylicum and C. beijerinckii, as well as the gas-fermenting C. ljungdahlii. On this basis, future directions in the study and remodeling of clostridial regulation systems, were proposed for effective modification of these industrially important anaerobes.

Authors:Daxi Wang; Pasi K. Korhonen; Robin B. Gasser; Neil D. YoungAbstract: Publication date: Available online 15 February 2018 Source:Biotechnology Advances Author(s): Daxi Wang, Pasi K. Korhonen, Robin B. Gasser, Neil D. Young Clonorchis sinensis (family Opisthorchiidae) is an important foodborne parasite that has a major socioeconomic impact on ~35 million people predominantly in China, Vietnam, Korea and the Russian Far East. In humans, infection with C. sinensis causes clonorchiasis, a complex hepatobiliary disease that can induce cholangiocarcinoma (CCA), a malignant cancer of the bile ducts. Central to understanding the epidemiology of this disease is knowledge of genetic variation within and among populations of this parasite. Although most published molecular studies seem to suggest that C. sinensis represents a single species, evidence of karyotypic variation within C. sinensis and cryptic species within a related opisthorchiid fluke (Opisthorchis viverrini) emphasise the importance of studying and comparing the genes and genomes of geographically distinct isolates of C. sinensis. Recently, we sequenced, assembled and characterised a draft nuclear genome of a C. sinensis isolate from Korea and compared it with a published draft genome of a Chinese isolate of this species using a bioinformatic workflow established for comparing draft genome assemblies and their gene annotations. We identified that 50.6% and 52.1% of the Korean and Chinese C. sinensis genomic scaffolds were syntenic, respectively. Within aligned syntenic blocks, the genomes had a high level of nucleotide identity (99.1%) and encoded 15 variable proteins likely to be involved in diverse biological processes. Here, we review current technical challenges of using draft genome assemblies to undertake comparative genomic analyses to quantify genetic variation between isolates of the same species. Using a workflow that overcomes these challenges, we report on a high-quality draft genome for C. sinensis from Korea and comparative genomic analyses, as a basis for future investigations of the genetic structures of C. sinensis populations, and discuss the biotechnological implications of these explorations.

Authors:Andreas Koeberle; Oliver WerzAbstract: Publication date: Available online 15 February 2018 Source:Biotechnology Advances Author(s): Andreas Koeberle, Oliver Werz Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit prostanoid formation and represent prevalent therapeutics for treatment of inflammatory disorders. However, NSAIDs are afflicted with severe side effects, which might be circumvented by more selective suppression of pro-inflammatory eicosanoid biosynthesis. This concept led to dual inhibitors of microsomal prostaglandin E2 synthase (mPGES)-1 and 5-lipoxygenase that are crucial enzymes in the biosynthesis of pro-inflammatory prostaglandin E2 and leukotrienes. The potential of their dual inhibition in light of superior efficacy and safety is discussed. Focus is placed on natural products, for which direct inhibition of mPGES-1 and leukotriene biosynthesis has been confirmed.

Authors:Neerajha Nagarajan; Agnes Dupret-Bories; Erdem Karabulut; Pinar Zorlutuna; Nihal Engin VranaAbstract: Publication date: Available online 9 February 2018 Source:Biotechnology Advances Author(s): Neerajha Nagarajan, Agnes Dupret-Bories, Erdem Karabulut, Pinar Zorlutuna, Nihal Engin Vrana The impact of additive manufacturing in our lives has been increasing constantly. One of the frontiers in this change is the medical devices. 3D printing technologies not only enable the personalization of implantable devices with respect to patient-specific anatomy, pathology and biomechanical properties but they also provide new opportunities in related areas such as surgical education, minimally invasive diagnosis, medical research and disease models. In this review, we cover the recent clinical applications of 3D printing with a particular focus on implantable devices. The current technical bottlenecks in 3D printing in view of the needs in clinical applications are explained and recent advances to overcome these challenges are presented. 3D printing with cells (bioprinting); an exciting subfield of 3D printing, is covered in the context of tissue engineering and regenerative medicine and current developments in bioinks are discussed. Also emerging applications of bioprinting beyond health, such as biorobotics and soft robotics, are introduced. As the technical challenges related to printing rate, precision and cost are steadily being solved, it can be envisioned that 3D printers will become common on-site instruments in medical practice with the possibility of custom-made, on-demand implants and, eventually, tissue engineered organs with active parts developed with biorobotics techniques.

Authors:M. Teresa Cesário; M. Manuela R. da Fonseca; Mafalda M. Marques; M. Catarina M.D. de AlmeidaAbstract: Publication date: Available online 9 February 2018 Source:Biotechnology Advances Author(s): M.T. Cesário, M.M.R. da Fonseca, M.M. Marques, M.C.M.D. de Almeida The high content of lipids in microalgae (>60% w/w in some species) and of carbohydrates in seaweed (up to 75%) have promoted intensive research towards valorisation of algal components for the production of biofuels. However, the exploitation of the carbohydrate fraction to produce a range of chemicals and chemical intermediates with established markets is still limited. These include organic acids (e.g. succinic and lactic acid), alcohols other than bioethanol (e.g. butanol), and biomaterials (e.g. polyhydroxyalkanoates). This review highlights current and potential applications of the marine algal carbohydrate fractions as major C-source for microbial production of biomaterials and building blocks.

Authors:Irini Angelidaki; Laura Treu; Panagiotis Tsapekos; Gang Luo; Stefano Campanaro; Henrik Wenzel; Panagiotis G. KougiasAbstract: Publication date: Available online 3 February 2018 Source:Biotechnology Advances Author(s): Irini Angelidaki, Laura Treu, Panagiotis Tsapekos, Gang Luo, Stefano Campanaro, Henrik Wenzel, Panagiotis G. Kougias Biogas production is an established sustainable process for simultaneous generation of renewable energy and treatment of organic wastes. The increasing interest of utilizing biogas as substitute to natural gas or its exploitation as transport fuel opened new avenues in the development of biogas upgrading techniques. The present work is a critical review that summarizes state-of-the-art technologies for biogas upgrading and enhancement with particular attention to the emerging biological methanation processes. The review includes comprehensive description of the main principles of various biogas upgrading methodologies, scientific and technical outcomes related to their biomethanation efficiency, challenges that have to be addressed for further development and incentives and feasibility of the upgrading concepts.

Authors:Iveta BernatovaAbstract: Publication date: Available online 2 February 2018 Source:Biotechnology Advances Author(s): Iveta Bernatova Recent studies have suggested that certain (−)-epicatechin-containing foods have a blood pressure-lowering capacity. The mechanisms underlying (−)-epicatechin action may help prevent oxidative damage and endothelial dysfunction, which have both been associated with hypertension and certain brain disorders. Moreover, (−)-epicatechin has been shown to modify metabolic profile, blood's rheological properties, and to cross the blood-brain barrier. Thus, (−)-epicatechin causes multiple actions that may provide unique synergy beneficial for cardiovascular and neuropsychological health. This review summarises the current knowledge on the biological actions of (−)-epicatechin, related to cardiovascular and brain functions, which may play a remarkable role in human health and longevity.

Authors:Cuitlahuac Chavez-Pena; Amine A. KamenAbstract: Publication date: Available online 1 February 2018 Source:Biotechnology Advances Author(s): Cuitlahuac Chavez-Pena, Amine A. Kamen The baculovirus expression vector system (BEVS) is a popular manufacturing platform for the production of recombinant proteins, antiviral vaccines, gene therapy vectors, and biopesticides. Besides its successful applications in the industrial sector, the system has also played a significant role within the academic community given its extensive use in the production of hard-to-express eukaryotic multiprotein complexes for structural characterization for example. However, as other expression platforms, BEVS has to be continually improved to overcome its limitation and adapt to the constant demand for manufacturing processes that provide recombinant products with improved quality at higher yields and lower production cost. RNA interference, or RNAi, is a relatively recent technology that has revolutionized how scientist study gene function. Originally introduced as a tool to study biological and disease-related processes it has recently been applied to improve the yield and quality of recombinant proteins produced in several expression systems. In this review, we provide a comprehensive summary of the impact that RNAi-mediated silencing of cellular or viral genes in the BEVS has on the production of recombinant products. We also propose a critical analysis of several aspects of the methodologies described in the literature for the use of RNAi technology in the BEVS with the intent to provide the reader with eventually useful guidance for designing experiments.

Authors:Maysam Mansouri; Philipp BergerAbstract: Publication date: Available online 31 January 2018 Source:Biotechnology Advances Author(s): Maysam Mansouri, Philipp Berger Systems for multigene delivery in mammalian cells, particularly in the context of genome engineering, have gained a lot of attention in biomolecular research and medicine. Initially these methods were based on RNA polymerase II promoters and were used for the production of protein complexes and for applications in cell biology such as reprogramming of somatic cells to stem cells. Emerging technologies such as CRISPR/Cas9-based genome engineering, which enable any alteration at the genomic level of an organism, require additional elements including U6-driven expression cassettes for RNA expression and homology constructs for designed genome modifications. For these applications, systems with high DNA capacity, flexibility and transfer rates are needed. In this article, we briefly give an update on some of recent strategies that facilitate multigene assembly and delivery into mammalian cells. Also, we review applications in various fields of biology that rely on multigene delivery systems.

Authors:Sureshkumar Kempahanumakkagari; Vanish Kumar; Pallabi Samaddar; Pawan Kumar; Thippeswamy Ramakrishnappa; Ki-Hyun KimAbstract: Publication date: Available online 31 January 2018 Source:Biotechnology Advances Author(s): Sureshkumar Kempahanumakkagari, Vanish Kumar, Pallabi Samaddar, Pawan Kumar, Thippeswamy Ramakrishnappa, Ki-Hyun Kim Technological advancements combined with materials research have led to the generation of enormous types of novel substrates and materials for use in various biological/medical, energy, and environmental applications. Lately, the embedding of biomolecules in novel and/or advanced materials (e.g., metal-organic frameworks (MOFs), nanoparticles, hydrogels, graphene, and their hybrid composites) has become a vital research area in the construction of an innovative platform for various applications including sensors (or biosensors), biofuel cells, and bioelectronic devices. Due to the intriguing properties of MOFs (e.g., framework architecture, topology, and optical properties), they have contributed considerably to recent progresses in enzymatic catalysis, antibody-antigen interactions, or many other related approaches. Here, we aim to describe the different strategies for the design and synthesis of diverse biomolecule-embedded MOFs for various sensing (e.g., optical, electrochemical, biological, and miscellaneous) techniques. Additionally, the benefits and future prospective of MOFs-based biomolecular immobilization as an innovative sensing platform are discussed along with the evaluation on their performance to seek for further development in this emerging research area.

Authors:Vilém Zachleder; Milada Vítová; Monika Hlavová; Šárka Moudříková; Peter Mojzeš; Hermann Heumann; Johannes R. Becher; Kateřina BišováAbstract: Publication date: Available online 19 January 2018 Source:Biotechnology Advances Author(s): Vilém Zachleder, Milada Vítová, Monika Hlavová, Šárka Moudříková, Peter Mojzeš, Hermann Heumann, Johannes R. Becher, Kateřina Bišová Stable isotopes are used in wide fields of application from natural tracers in biology, geology and archeology through studies of metabolic fluxes to their application as tracers in quantitative proteomics and structural biology. We review the use of stable isotopes of biogenic elements (H, C, N, O, S, Mg, Se) with the emphasis on hydrogen and its heavy isotope deuterium. We will discuss the limitations of enriching various compounds in stable isotopes when produced in living organisms. Finally, we overview methods for measuring stable isotopes, focusing on methods for detection in single cells in situ and their exploitation in modern biotechnologies.

Authors:Jaroslav Zelenka; Martina Koncošová; Tomáš RumlAbstract: Publication date: Available online 12 January 2018 Source:Biotechnology Advances Author(s): Jaroslav Zelenka, Martina Koncošová, Tomáš Ruml The hallmarks of tumor tissue are not only genetic aberrations but also the presence of metabolic and oxidative stress as a result of hypoxia and lactic acidosis. The stress activates several prosurvival pathways including metabolic remodeling, autophagy, antioxidant response, mitohormesis, and glutaminolysis, whose upregulation in tumors is associated with a poor survival of patients, while their activation in healthy tissue with statins, metformin, physical activity, and natural compounds prevents carcinogenesis. This review emphasizes the dual role of stress response pathways in cancer and suggests the integrative understanding as a basis for the development of rational therapy targeting the stress response.

Authors:Guodong Luan; Xuefeng LuAbstract: Publication date: Available online 10 January 2018 Source:Biotechnology Advances Author(s): Guodong Luan, Xuefeng Lu Photosynthetic biomanufacturing provides a promising solution for sustainable production of biofuels and biochemicals. Cyanobacteria are among the most promising microbial platforms for the construction of photosynthetic cell factories. Metabolic engineering of cyanobacteria has enabled effective photosynthetic synthesis of diverse natural or non-natural metabolites, while commercialization of photosynthetic biomanufacturing is usually restricted by process and economic feasibilities. In actual outdoor conditions, active cell growth and product synthesis is restricted to narrow light exposure windows of the day-night cycles and is threatened by diverse physical, chemical, and biological environmental stresses. For biomass harvesting and bioproduct recovery, energy and cost consuming processing and equipment is required, which further decreases the economic and environmental competitiveness of the entire process. To facilitate scaled photosynthetic biomanufacturing, lots of efforts have been made to engineer cyanobacterial cell properties required by robust & continual cultivation and convenient & efficient recovery. In this review, we specifically summarized recently reported engineering strategies on optimizing industrial properties of cyanobacterial cells. Through systematically re-editing the metabolism, morphology, mutualism interaction of cyanobacterial chassis cells, the adaptabilities and compatibilities of the cyanobacterial cell factories to the industrial process could be significantly improved. Cell growth and product synthesis of the tailored cyanobacterial cells could be expanded and maintained at night and in stressful environments, while convenient biomass harvesting could also be expected. For developing more feasible cyanobacterial photosynthetic biomanufacturing in large scale, we here propose the importance of tailoring industrial properties of cyanobacteria and outline the directions that should be exploited in the future.

Authors:Bárbara Gomes; Marcelo T. Augusto; Mário R. Felício; Axel Hollmann; Octávio L. Franco; Sónia Gonçalves; Nuno C. SantosAbstract: Publication date: Available online 9 January 2018 Source:Biotechnology Advances Author(s): Bárbara Gomes, Marcelo T. Augusto, Mário R. Felício, Axel Hollmann, Octávio L. Franco, Sónia Gonçalves, Nuno C. Santos Infectious diseases are one of the main causes of human morbidity and mortality. In the last few decades, pathogenic microorganisms' resistance to conventional drugs has been increasing, and it is now pinpointed as a major worldwide health concern. The need to search for new therapeutic options, as well as improved treatment outcomes, has therefore increased significantly, with biologically active peptides representing a new alternative. A substantial research effort is being dedicated towards their development, especially due to improved biocompatibility and target selectivity. However, the inherent limitations of peptide drugs are restricting their application. In this review, we summarize the current status of peptide drug development, focusing on antiviral and antimicrobial peptide activities, highlighting the design improvements needed, and those already being used, to overcome the drawbacks of the therapeutic application of biologically active peptides.

Authors:Francesca Berini; Chen Katz; Nady Gruzdev; Morena Casartelli; Gianluca Tettamanti; Flavia MarinelliAbstract: Publication date: Available online 4 January 2018 Source:Biotechnology Advances Author(s): Francesca Berini, Chen Katz, Nady Gruzdev, Morena Casartelli, Gianluca Tettamanti, Flavia Marinelli The negative impact of the massive use of synthetic pesticides on the environment and on human health has stimulated the search for environment-friendly practices for controlling plant diseases and pests. Among them, biocontrol, which relies on using beneficial organisms or their products (bioactive molecules and/or hydrolytic enzymes), holds the greatest promise and is considered a pillar of integrated pest management. Chitinases are particularly attractive to this purpose since they have fungicidal, insecticidal, and nematicidal activities. Here, current knowledge on the biopesticidal action of microbial and viral chitinases is reviewed, together with a critical analysis of their future development as biopesticides.

Authors:Ammad Ahmad Farooqi; Nishil N. Desai; Muhammad Zahid Qureshi; Daniele Rubert Nogueira Librelotto; Maria Luisa Gasparri; Anupam Bishayee; Seyed Mohammad Nabavi; Valeria Curti; Maria DagliaAbstract: Publication date: Available online 14 December 2017 Source:Biotechnology Advances Author(s): Ammad Ahmad Farooqi, Nishil N. Desai, Muhammad Zahid Qureshi, Daniele Rubert Nogueira Librelotto, Maria Luisa Gasparri, Anupam Bishayee, Seyed Mohammad Nabavi, Valeria Curti, Maria Daglia A rapidly growing body of experimental evidence has begun to shed light on the wide ranging molecular mechanisms which modulate intra- and inter-cellular communications. A substantial quantity of the available knowledge has only been uncovered in recent years, and we are learning that donor cells release nanovesicles, known as exosomes, which regulate the cellular behavior of recipient cells following uptake. Based on the impressive capacity of exosomes in delivering their “payload”, different therapeutic agents, are currently being tested using this delivery method for more effective therapy. This review summarizes the most recent developments in exosome bioactivities and discusses the biochemical nature of exosomes and their biogenesis. It also summarizes the use of exosomes as delivery vehicles for drugs and natural compounds to the targeted site.

Authors:Yugyung Lee; Chi H. LeeAbstract: Publication date: Available online 14 December 2017 Source:Biotechnology Advances Author(s): Yugyung Lee, Chi H. Lee As our understanding of onset and progress of diseases at the genetic and molecular level rapidly progresses, the potential of advanced technologies, such as 3D-printing, Socially-Assistive Robots (SARs) or augmented reality (AR), that are applied to personalized nanomedicines (PNMs) to alleviate pathological conditions, has become more prominent. Among advanced technologies, AR in particular has the greatest potential to address those challenges and facilitate the translation of PNMs into formidable clinical application of personalized therapy. As AR is about to adapt additional new methods, such as speech, voice recognition, eye tracing and motion tracking, to enable interaction with host response or biological systems in 3-D space, a combination of multiple approaches to accommodate varying environmental conditions, such as public noise and atmosphere brightness, will be explored to improve its therapeutic outcomes in clinical applications. For instance, AR glasses still being developed by Facebook or Microsoft will serve as new platform that can provide people with the health information they are interested in or various measures through which they can interact with medical services. This review has addressed the current progress and impact of AR on PNMs and its application to the biomedical field. Special emphasis is placed on the application of AR based PNMs to the treatment strategies against senior care, drug addiction and medication adherence.

Authors:Masaharu Murata; Jeong-Hun KangAbstract: Publication date: Available online 8 December 2017 Source:Biotechnology Advances Author(s): Masaharu Murata, Jeong-Hun Kang Bisphenol A (BPA; 4,4′-isopropylidenediphenol) is an endocrine disruptor that is used as a material for the production of phenol resins, polyacrylates, polyesters, epoxy resins, and polycarbonate plastics. Endocrine-disruptive or toxic effects of BPA on living organisms through a number of cell signaling pathways have been reported. BPA induces carcinogenesis, reproductive toxicity, abnormal inflammatory or immune response, and developmental disorders of brain or nervous system through various cell signaling pathways. This review considers the literature concerning BPA and its association with cancer-related cell signaling pathways, reproductive toxicity-related cell signaling pathways, inflammatory or immune response-related cell signaling pathways, and brain and nervous system-related cell signaling pathways.

Authors:Carla Giles; Stephanie J. Lamont-Friedrich; Thomas D. Michl; Hans J. Griesser; Bryan R. CoadAbstract: Publication date: Available online 2 December 2017 Source:Biotechnology Advances Author(s): Carla Giles, Stephanie J. Lamont-Friedrich, Thomas D. Michl, Hans J. Griesser, Bryan R. Coad In recent years, increasing evidence has been collated on the contributions of fungal species, particularly Candida, to medical device infections. Fungal species can form biofilms by themselves or by participating in polymicrobial biofilms with bacteria. Thus, there is a clear need for effective preventative measures, such as thin coatings that can be applied onto medical devices to stop the attachment, proliferation, and formation of device-associated biofilms. However, fungi being eukaryotes, the challenge is greater than for bacterial infections because antifungal agents are often toxic towards eukaryotic host cells. Whilst there is extensive literature on antibacterial coatings, a far lesser body of literature exists on surfaces or coatings that prevent attachment and biofilm formation on medical devices by fungal pathogens. Here we review strategies for the design and fabrication of medical devices with antifungal surfaces. We also survey the microbiology literature on fundamental mechanisms by which fungi attach and spread on natural and synthetic surfaces. Research in this field requires close collaboration between biomaterials scientists, microbiologists and clinicians; we consider progress in the molecular understanding of fungal recognition of, and attachment to, suitable surfaces, and of ensuing metabolic changes, to be essential for designing rational approaches towards effective antifungal coatings, rather than empirical trial of coatings.

Authors:Nina Henry; Johann Clouet; Jean Le Bideau; Catherine Le Visage; Jérôme GuicheuxAbstract: Publication date: Available online 1 December 2017 Source:Biotechnology Advances Author(s): Nina Henry, Johann Clouet, Jean Le Bideau, Catherine Le Visage, Jérôme Guicheux As our understanding of the physiopathology of intervertebral disc (IVD) degeneration has improved, novel therapeutic strategies have emerged, based on the local injection of cells, bioactive molecules, and nucleic acids. However, with regard to the harsh environment constituted by degenerated IVDs, protecting biologics from in situ degradation while allowing their long-term delivery is a major challenge. Yet, the design of the optimal approach for IVD regeneration is still under debate and only a few papers provide a critical assessment of IVD-specific carriers for local and sustained delivery of biologics. In this review, we highlight the IVD-relevant polymers as well as their design as macro-, micro-, and nano-sized particles to promote endogenous repair. Finally, we illustrate how multiscale systems, combining in situ-forming hydrogels with ready-to-use particles, might drive IVD regenerative medicine strategies toward innovation.